Catecholamine neurotransmitters (dopamine, norepinephrine, and epinephrine) are synthesized in catecholaminergic neurons from tyrosine, via dopa, dopamine, and norepinephrine, to epinephrine. Four enzymes are involved in the biosynthesis of epinephrine: (1) tyrosine 3-mono-oxygenase (tyrosine hydroxylase, TH); (2) aromatic L-amino acid decarboxylase (AADC, or DOPA decarboxylase, DDC); (3) dopamine beta-mono-oxygenase (dopamine beta-hydroxylase, DBH); and (4) phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28). PNMT is a cytosolic enzyme that catalyzes the synthesis of epinephrine from norepinephrine. PNMT is expressed in chromaffin cells of the adrenal medulla, medulla oblongata, hypothalamus, and sensory nuclei of the vagus nerve. The gene encoding PNMT maps to a region of the human genome that is associated with multiple sclerosis, and polymorphisms within the promoter of the PNMT gene are associated with multiple sclerosis. Polymorphisms in the promoter of the PNMT gene also have been implicated in early-onset Alzheimer's disease.